Safety and efficacy of an oral insulin (Capsulin) in patients with early-stage type 2 diabetes: A dose-ranging phase 2b study

Aim

To compare the pharmacodynamic properties of different doses of regular human insulin administered in capsule form twice daily in a randomised twelve-week open-label study.

Methods

A total of 100 individuals (48 males, 52 females) with type 2 diabetes on metformin completed the study according to the protocol. The mean (SD) age was 48.5 (6.7) years, body mass index 25.7 (2.8) kg/m² and HbA1c 8.10% (0.65%). Subjects randomized upon admission were assigned to one of three groups receiving formulated regular insulin at dose levels of 75 iu BD, 150 iu insulin BD, or 300 iu BD, all in enteric-coated capsules. The primary and secondary endpoints were change from baseline in HbA1c and fasting plasma glucose (FPG), respectively.

Results

The study met its primary clinical endpoint of a decrease in HbA1c of 0.5% or higher (least square mean decrease 0.52%; P = .004, median decrease 0.6%) in the dose group receiving 150 iu BD. In a subset of this population, with starting HbA1c values of 9% to 9.5%, an average decrease of 1.575% was observed. In the total population, least square mean decreases in HbA1c for the 75 and 300 iu BD groups were −0.11% and −0.42%, respectively. Mean change in FPG in the 150 iu BD dose group was −18.8 mg/dl (P = .017) and −14.8 and −2.7 mg/dl for the 75 and 300 iu BD groups, respectively. A decrease of 20% for triglycerides (−40 mg/dl) was observed in the 150 iu BD dose group. No significant increases in body weight were observed, and significant decreases in systolic blood pressure were seen in all groups. No serious treatment-related adverse events were recorded, and no incidence of hypoglycaemia was reported throughout the entire 12-week study period.

Conclusions

Capsulin oral insulin administered twice per day at a dose of 150 iu per capsule is safe, with no confirmed treatment-linked hypoglycaemic events, and results in significant decreases from baseline in HbA1c, FPG and triglycerides.